Professor David Tremethick, Head of Genome Biology Department, The John Curtin School of Medical Research, The Australian National University.

Photo: Australian National University

The epigenetic regulator H2A.B

It is now clearly established that the central regulator of eukaryotic gene expression is the organization of the genome into chromatin. Chromatin performs this crucial function by partitioning the genome into domains that are either open and transcriptionally active or closed and repressed.

Chromatin is built from nucleosomes (histones plus DNA), the universal repeating protein-DNA complex in all eukaryotic cells. Nucleosome function is dependent upon the composition of the underlying nucleosome. The key way the biochemical composition of the nucleosome is altered is by the substitution of one or more of the core histones with the corresponding histone variant.

Previously, we discovered a new histone variant, H2A.B that displays a unique tissue expression pattern i.e. it is expressed in the testis and the brain.

In order to gain mechanistic insights into the role of H2A.B.3 in these different tissues, we took a proteomic approach to identify proteins that specifically interact with H2A.B-containing nucleosomes, analysed its pattern of organisation and expression, uncovered its genomic locations and its relationship with other epigenetic marks, analysed an unexpected interaction with RNA both in vivo and in vitro and most recently, generated a H2A.B mouse knockout.

Our data thus far allows us to propose that H2A.B participates in a novel gene activation and pre-mRNA splicing mechanism that operates uniquely in the testis and brain.

About the speaker

Prof. Tremethick received his PhD from Macquarie University and CSIRO in Sydney, where he studied the role of chromosomal proteins in regulating transcription. With an NIH Fogarty Fellowship he did a post-doc at the University of Rochester, New York, where he developed an in vitro chromatin assembly system to study how chromatin regulates gene activation. He returned to Australia and established his lab at the John Curtin School of Medical Research at the ANU in 1993, where he is today Full Professor and heads the Genome Biology Department.

The aim of his group is to link chromatin structure to the control of cell differentiation by studying histone variants. His lab has established several complex in vitro, biophysical and genome-wide techniques, and has used several model systems ranging from Drosophila genetics to mouse embryology, including mouse spermatogenesis.

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